A Phase II Trial With Pemetrexed Plus Cisplatin as First Line Chemotherapy for Advanced Non - Small Cell Lung Cancer (NSCLC) Patients With Measurable Asymptomatic Brain Metastasis (GFPC 07-01/METAL).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 25
- 主要终点
- Objective of this study is overall response rate on brain metastasis according to RECIST criteria.
研究概览
简要总结
NSCLC patients often have cerebral metastasis : 10% at diagnosis and 40% during disease management. Neurosurgery is not indicated in the majority of cases because of presence of several lesions in the brain, failure of primary tumor control or presence of extra-cerebral metastasis. Cerebral metastasis lead to death in 30 to 50% of these cases. Management of these patients in this situation is based on supportive care and whole-brain radiotherapy. The place of chemotherapy for patients with good performance status was discussed for a long time and it is now admitted. However, the place of new drugs such as pemetrexed, which is currently used as a second line treatment for NSCLC, needs to be further studied. It is known that pemetrexed when added to cisplatin for treatment of NSCLC provides a similar effectiveness when compared to other drugs associations commonly used in this indication. In addition, Cisplatin with Pemetrexed probably present a better safety profile.
The present study is based upon the hypothesis stipulating that the association cisplatin-pemetrexed will be at least as efficient as the others association currently used for treatment of NSCLC and will present a better safety profile. The primary objective of this study is overall response rate on brain metastasis according to RECIST criteria. Secondary judgment criterias are : Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms, overall survival.
The trial will enroll up to 45 patients in this single-arm two-stage sequential phase II study with the possibility of stopping the study early because of lack of efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with cytologically or histologically confirmed NSCLC.
- •Patient with brain metastasis not amenable to surgery or radiosurgery with curative intent
- •At least one brain measurable lesion using RECIST criteria
- •ECOG Performance Status ≤2
- •No prior chemotherapy for this cancer
- •Prior surgery is allowed provided there is a relapse or progression after the procedure.
- •Adequate organ function including the following: Adequate bone marrow reserve: absolute neutrophil count (ANC) superior or equal to 1.5 X109/L, platelets superior or equal to 100 X 109/L, and hemoglobin superior or equal to 9 g/dL; Hepatic: bilirubin <1.5 times the upper limit of normal (ULN), alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) <3xULN (or <5xULN with liver metastases); Renal: Calculated creatinine clearance (CrCl) superior or equal to 45mL/min based on the standard Cockroft and Gault formula
- •Signed informed consent document from the patient
- •Patient must be at least 18 years of age.
- •Estimated life expectancy of at least 12 weeks.
- •Effective contraception (men and women) for and during the 6 months following the end of treatment
排除标准
- •Symptomatic brain metastasis
- •Have received prior radiotherapy for brain metastasis
- •Unable or unwilling to take folic acid, vitamin B12 supplementation or dexamethasone (or equivalent corticosteroid); or any other inability to comply with protocol or study related procedures.
- •A prior malignancy other than NSCLC, except carcinoma in situ of the cervix or non-melanoma skin cancer, adequately treated low grade [Gleason score <6] localized prostate cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence
- •Serious concomitant systemic disorders (for example, active infection or abnormal electrocardiogram (ECG) indicative of cardiac disease) that, in the opinion of the investigator, would compromise the safety of the patient and his/her ability to complete study.
- •Inability to discontinue administration of aspirin at a dose >1.3g/day or other non-steroidal anti-inflammatory agents for 2 days before, the day of, and 2 days after the dose of pemetrexed (5 days prior for long-acting agents such as piroxicam).
- •Presence of fluid accumulations in third spaces, e.g., ascite or pleural effusion, which can be detected clinically (during physical examination), and which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
- •Peripheral neuropathy > CTC Grade 2
- •Patient compliance or geographic distance precluding adequate follow up.
研究组 & 干预措施
A
干预措施: Pemetrexed, cisplatin (Drug)
结局指标
主要结局
Objective of this study is overall response rate on brain metastasis according to RECIST criteria.
时间窗: After cycles 2, 4 and 6 and every 6 weeks after study drug completion in absence of disease progression.
次要结局
- Overall response rate, PFS after first-line CDDP plus pemetrexed, safety profile, quality of life, neurological symptoms and overall survival.(After cycles 2, 4 and 6 and every 6 weeks after study drug completion.)